Remote Memory Research Articles

D1 Receptor Mediated Dopaminergic Neurotransmission Facilitates Remote Memory of Contextual Fear Conditioning.

Dopaminergic neurotransmission via dopamine D1 receptors (D1Rs) is considered to play an important role not only in reward-based learning but also in aversive learning. The contextual and auditory cued fear conditioning tests involve the processing of classical fear conditioning and evaluates aversive learning memory. It is possible to evaluate aversive learning memory in two different types of neural transmission circuits. In addition, when evaluating the role of dopaminergic neurotransmission via D1R, to avoid the effects in D1R-mediated neural circuitry alterations during development, it is important to examine using mice who D1R expression in the mature stage is suppressed. Herein, we investigated the role of dopaminergic neurotransmission via D1Rs in aversive memory formation in contextual and auditory cued fear conditioning tests using D1R knockdown (KD) mice, in which the expression of D1Rs could be conditionally and reversibly controlled with doxycycline (Dox) treatment. For aversive memory, we examined memory formation using recent memory 1 day after conditioning, and remote memory 4 weeks after conditioning. Furthermore, immunostaining of the brain tissues of D1RKD mice was performed after aversive footshock stimulation to investigate the distribution of activated c-Fos, an immediate-early gene, in the hippocampus (CA1, CA3, dentate gyrus), striatum, amygdala, and prefrontal cortex during aversive memory formation. After aversive footshock stimulation, immunoblotting was performed using hippocampal, striatal, and amygdalar samples from D1RKD mice to investigate the increase in the amount of c-Fos and phosphorylated SNAP-25 at Ser187 residue. When D1R expression was suppressed using Dox, behavioral experiments revealed impaired contextual fear learning in remote aversion memory following footshock stimulation. Furthermore, expression analysis showed a slight increase in the post-stimulation amount of c-Fos in the hippocampus and striatum, and a significant increase in the amount of phosphorylated SNAP-25 in the hippocampus, striatum, and prefrontal cortex before and after stimulation. These findings indicate that deficiency in D1R-mediated dopaminergic neurotransmission is an important factor in impairing contextual fear memory formation for remote memory.

LogSC: Model-based one-sided communication performance estimation

One-sided communication (also known as remote memory access, or RMA) in the Message Passing Interface (MPI) is a communication interface that has been introduced in MPI-2 (1997) that enables new more efficient programming models. In MPI-3, some new more flexible and efficient primitives have been introduced, which makes it easier to use and more deployable.However, compared to traditional two-sided communication, little work has been performed on analyzing one-sided communication costs, which urgently requires formal analysis. The communication performance model is a formal analysis of communication and its cost. We focus on the software model, whose core idea is that the transmission can be represented as a sequence of implicit transfers and data movements. This approach is a suitable solution for concurrent communication modeling.We propose LogSC, which consists of the window cost, transmission cost, synchronization cost, and computational cost in atomic operations. In this paper, LogSC is used to model most of the operations in one-sided communication, including the put/get operation, atomic operation, and shared memory programming of MPI. We model and evaluate the parallel tests of IMB, collectives designed by combining MPI and the MPI shared memory (MPI+MPI), and the communication in the scalable universal matrix multiplication algorithm (SUMMA), which is a common matrix multiplication algorithm. Experiments show that our modeling has high accuracy, which makes up for the lack of existing models.

Deterministic Time-Bin Entanglement between a Single Photon and an Atomic Ensemble.

Hybrid matter-photon entanglement is the building block for quantum networks. It is very favorable if the entanglement can be prepared with a high probability. In this Letter, we report the deterministic creation of entanglement between an atomic ensemble and a single photon by harnessing the Rydberg blockade. We design a scheme that creates entanglement between a single photon's temporal modes and the Rydberg levels that host a collective excitation, using a process of cyclical retrieving and patching. The hybrid entanglement is tested via retrieving the atomic excitation as a second photon and performing correlation measurements, which suggest an entanglement fidelity of 87.8%. Our source of matter-photon entanglement will enable the entangling of remote quantum memories with much higher efficiency.

Differential Recruitment of the Infralimbic Cortex in Recent and Remote Retrieval and Extinction of Aversive Memory in Post-Weanling Rats.

BackgroundWe previously showed that the infralimbic medial prefrontal cortex (IL-mPFC) plays an important role in recent and remote memory retrieval and extinction of conditioned odor aversion (COA) and contextual fear conditioning (CFC) in adult rats. Because the mPFC undergoes maturation during post-weaning, here, we aimed to explore (1) whether post-weanling rats can form recent and remote COA and CFC memory, and (2) the role of the IL-mPFC in mediating these processes.MethodsTo investigate the retrieval process, we transiently inactivated the IL-mPFC with lidocaine prior to the retrieval test at either recent or remote time points. To target the consolidation process, we applied the protein synthesis inhibitor after the retrieval at recent or remote time points.ResultsOur results show that the post-weanling animals were able to develop both recent and remote memory of both COA and CFC. IL-mPFC manipulations had no effect on retrieval or extinction of recent and remote COA memory, suggesting that the IL has no effect in COA at this developmental stage. In contrast, the IL-mPFC played a role in (1) the extinction of recent, but not remote, CFC memory, and (2) the retrieval of remote, but not recent, CFC memory. Moreover, remote, but not recent, CFC retrieval enhanced c-Fos protein expression in the IL-mPFC.ConclusionsAltogether, these results point to a differential role of the IL-mPFC in recent and remote CFC memory retrieval and extinction and further confirm the differences in the role of IL-mPFC in these processes in post-weanling and adult animals.

Berberine Facilitates Extinction and Prevents the Return of Fear.

Exposure to a catastrophic event or intense stimulation can trigger fear memories, and the threatening memories persist even over a lifetime. Exposure therapy is based on extinction learning and is widely used to treat fear-related disorders, but its effect on remote fear memory is modest. Berberine, an isoquinoline alkaloid derived from Coptis chinensis or Berberis spp., has been recently reported to exert a diversity of pharmacological effects on the central nervous system, such as facilitating extinction of drug memory. Here, we explored the effect of berberine on extinction of fear memory using a classical contextual fear conditioning (CFC) paradigm, which is Pavlovian conditioning, can rapidly create fear memories related to contexts. Twenty-four hours or 30 days after CFC training, mice were subjected to context extinction (10 days) to extinguish their behaviors and treated with 12.5 or 25 mg/kg berberine intragastrically 1 or 6 h after each extinction session, followed by reinstatement and spontaneous recovery tests. The results showed that intragastric administration of 25 mg/kg berberine 1 h after extinction significantly promoted the extinction of recent and remote fear memories and prevented reinstatement and spontaneous recovery of extinguished fear in mice. These findings indicate that berberine combined with extinction training could serve as a promising novel avenue for the treatment of fear-related disorders.

Glucosylceramide synthase inhibition reduces ganglioside GM3 accumulation, alleviates amyloid neuropathology, and stabilizes remote contextual memory in a mouse model of Alzheimer\u2019s disease

BackgroundGangliosides are highly enriched in the brain and are critical for its normal development and function. However, in some rare neurometabolic diseases, a deficiency in lysosomal ganglioside hydrolysis is pathogenic and leads to early-onset neurodegeneration, neuroinflammation, demyelination, and dementia. Increasing evidence also suggests that more subtle ganglioside accumulation contributes to the pathogenesis of more common neurological disorders including Alzheimer’s disease (AD). Notably, ganglioside GM3 levels are elevated in the brains of AD patients and in several mouse models of AD, and plasma GM3 levels positively correlate with disease severity in AD patients.MethodsTg2576 AD model mice were fed chow formulated with a small molecule inhibitor of glucosylceramide synthase (GCSi) to determine whether reducing glycosphingolipid synthesis affected aberrant GM3 accumulation, amyloid burden, and disease manifestations in cognitive impairment. GM3 was measured with LC-MS, amyloid burden with ELISA and amyloid red staining, and memory was assessed using the contextual fear chamber test.ResultsGCSi mitigated soluble Aβ42 accumulation in the brains of AD model mice when treatment was started prophylactically. Remarkably, GCSi treatment also reduced soluble Aβ42 levels and amyloid plaque burden in aged (i.e., 70 weeks old) AD mice with preexisting neuropathology. Our analysis of contextual memory in Tg2576 mice showed that impairments in remote (cortical-dependent) memory consolidation preceded deficits in short-term (hippocampal-dependent) contextual memory, which was consistent with soluble Aβ42 accumulation occurring more rapidly in the cortex of AD mice compared to the hippocampus. Notably, GCSi treatment significantly stabilized remote memory consolidation in AD mice—especially in mice with enhanced cognitive training. This finding was consistent with GCSi treatment lowering aberrant GM3 accumulation in the cortex of AD mice.ConclusionsCollectively, our results indicate that glycosphingolipids regulated by GCS are important modulators of Aβ neuropathology and that glycosphingolipid homeostasis plays a critical role in the consolidation of remote memories.

Abstract TP19: Sex Differences In The Impact Of Stroke On Retrieval Of Remote Fear Memory And Mir20a-3p Treatment

Preamble: Stroke is the major cause of death and disability worldwide. In addition to the immediate disability, stroke also results in diffuse secondary damage to regions distal to the ischemic region. Here we used the contextual fear conditioning test to assess the integrated functioning of affective and cognitive circuits after stroke in males and females, as well as the impact of mir20a-3p on this long term behavior. Methodology: Middle-aged (acyclic) females and males were injected stereotaxically with endothelin-1 in the left middle cerebral artery (MCA) region to create an ischemic stroke. Mir20a-3p mimics or scrambled oligo was administered i.v. 4h and 24h after stroke. Tests of sensory motor function including adhesive tape removal (ART) were performed prior to and after stroke. Long term cognitive changes were assessed by contextual fear conditioning (CFC) and the novel object recognition test (NORT). Results: Sensory motor deficits induced by stroke were abrogated with mir20a-3p treatment in both sexes. Contextual fear conditioning was evaluated by percent freezing during acquisition, extinction and retrieval. Sex differences were noted in fear extinction even prior to stroke, with males displaying resistance to extinction. At 30 days post-stroke, % freezing was no different from the pre-stroke extinction in females, while males showed a significant decrease in freezing rates after stroke, irrespective of treatment. In females, remote fear memory retrieval was reduced in vehicle-treated stroke rats, while the mir20a-3p treated group did not differ significantly from their pre-stroke levels. In contrast, both vehicle and mir20a-3p treated males showed a significant decline in freezing in response to fear retrieval. In female vehicle treated rats, the retrieval of remote fear memory continued to be impaired even at 100d post stroke(p<0.05), but preserved in miR20a-3p treatment group, indicating a persistent cognitive impairment and treatment effect. Conclusion: While mir20a-3p treatment improved sensory motor performance in both sexes, fear related memories were better preserved in females at 30 days, suggesting that neuroprotectants may have similar effects in the short term but may diverge in a sex specific manner in the chronic phase.

The Use of a Computerized Cognitive Assessment to Improve the Efficiency of Primary Care Referrals to Memory Services: Protocol for the Accelerating Dementia Pathway Technologies (ADePT) Study.

BackgroundExisting primary care cognitive assessment tools are crude or time-consuming screening instruments which can only detect cognitive impairment when it is well established. Due to the COVID-19 pandemic, memory services have adapted to the new environment by moving to remote patient assessments to continue meeting service user demand. However, the remote use of cognitive assessments has been variable while there has been scant evaluation of the outcome of such a change in clinical practice. Emerging research in remote memory clinics has highlighted computerized cognitive tests, such as the Integrated Cognitive Assessment (ICA), as prominent candidates for adoption in clinical practice both during the pandemic and for post-COVID-19 implementation as part of health care innovation.ObjectiveThe aim of the Accelerating Dementia Pathway Technologies (ADePT) study is to develop a real-world evidence basis to support the adoption of ICA as an inexpensive screening tool for the detection of cognitive impairment to improve the efficiency of the dementia care pathway.MethodsPatients who have been referred to a memory clinic by a general practitioner (GP) are recruited. Participants complete the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome are compared with the specialist diagnosis obtained at the memory clinic. The clinical outcomes as well as National Health Service reference costing data will be used to assess the potential health and economic benefits of the use of the ICA in the dementia diagnosis pathway.ResultsThe ADePT study was funded in January 2020 by Innovate UK (Project Number 105837). As of September 2021, 86 participants have been recruited in the study, with 23 participants also completing a retest visit. Initially, the study was designed for in-person visits at the memory clinic; however, in light of the COVID-19 pandemic, the study was amended to allow remote as well as face-to-face visits. The study was also expanded from a single site to 4 sites in the United Kingdom. We expect results to be published by the second quarter of 2022.ConclusionsThe ADePT study aims to improve the efficiency of the dementia care pathway at its very beginning and supports systems integration at the intersection between primary and secondary care. The introduction of a standardized, self-administered, digital assessment tool for the timely detection of neurodegeneration as part of a decision support system that can signpost accordingly can reduce unnecessary referrals, service backlog, and assessment variability.Trial RegistrationISRCTN 16596456; https://www.isrctn.com/ISRCTN16596456International Registered Report Identifier (IRRID)DERR1-10.2196/34475

Remembering Carlos S. Alvarado

I have remote but clear memories about the first time that I met Carlos S. Alvarado. It was in 1972. He was 17 and I 19 years old. Let me explain why we met at so young an age. In 1972 I was a member of the Society for Psychical Research (SPR). By that time, I was intellectually precocious and had already read about 200 books and many journals on psychical research or parapsychology. However, I felt completely alone: Nobody in Puerto Rico seemed to know the academic literature on those subjects. Therefore, I wrote to the secretary of the SPR asking if there was another member in Puerto Rico. At last! Yes! A person by the name of Carlos S. Alvarado. My first reaction was of total elation. However, on second thought, I was nervous and hesitant. I expected to meet a much older person who, seeing my young age, would dismiss me. So I wrote to Carlos a long letter where I explained that I was a young person but with a very serious approach to parapsychology. Rapidly he replied to me (remember, by mail; there was no email then). He really surprised me when he told me that he was nearly two years younger than I was! Not only that, our mothers had been friends when they were younger! So, in that way, a friendship that extended for 49 years began. In this obituary, I want to concentrate my comments on those early years that were important in Carlos’ decision to study parapsychology and to dedicate his intellectual life to the subject.

Convergent Coding of Recent and Remote Fear Memory in the Basolateral Amygdala

BackgroundIn both rodents and humans, the basolateral amygdala (BLA) is essential for encoding and retrieving conditioned fear memories. Although the BLA is a putative storage site for these memories, recent evidence suggests that they become independent of the BLA with the passage of time. MethodsWe systematically examined the role for the BLA in the retrieval of recent (1 day) and remote (2 weeks) fear memory using optogenetic, electrophysiological, and calcium imaging methods in male and female Long-Evans rats. Critically, we used a behavioral design that permits within-subjects comparison of recent and remote memory at the same time point; freezing behavior served as the index of learned fear. ResultsWe found that BLA c-Fos expression was similar after the retrieval of recent or remote fear memories. Extracellular single-unit recordings in awake, behaving animals revealed that single BLA neurons exhibit robust increases in spike firing to both recent and remote conditioned stimuli. Fiber photometry recordings revealed that these patterns of activity emerge from principal neurons. Consistent with these results, optogenetic inhibition of BLA principal neurons impaired conditioned freezing to both recent and remote conditioned stimuli. There were no sex differences in any of the measures or manipulations. ConclusionsThese data reveal that BLA neurons encode both recent and remote fear memories, suggesting substantial overlap in the allocation of temporally distinct events. This may underlie the broad generalization of fear memories across both space and time. Ultimately, these results provide evidence that the BLA is a long-term storage site for emotional memories.

Abstract- Poster

Aim:The aim of the study was to compare the Neurocognitive impairment in patients with Alcohol Dependence Syndrome patient and Opioid Dependence Syndrome.Objectives:To compare the difference in the domains of neurocognitive assessment in Alcohol Dependence Syndrome with Opioid Dependence Syndrome.METHODS:Fifty patients each diagnosed either as alcohol dependence syndrome or opioid dependence syndrome were evaluated. The baseline demographic of both the groups were quite comparable according to their age, sex, background education, propensity of having an addiction. Clinical Institute withdrawal assessment for alcohol scale (CIWA-Ar) and clinical opiate withdrawal score (COWS), alcohol use disorders identification test, alcohol severity index was the evaluated at baseline in these patients accordingly. These patients were followed up for a period of one month in the outpatient department and re-evaluated on the same scales after the treatment.RESULTS:PGI-Memory Scale was evaluated for the memory components, there was a significant increase in all the domains from baseline to follow up in both the groups except remote memory which although improved a little but was statistically and clinically insignificant in both the groups. The patients had statistically significant and clinically meaningful improvements in the domains of mental balance, improvements in attention and concentration across both the groups. The retention capacity in the patients also improved after one month of treatment. There was not much reduction in remote memory domain at baseline and thus not much improvement in the same at follow-up. This shows that remote memory is not significantly affected in both alcohol and opioid dependencies.Although improvements were seen from baseline to follow-up individually in both the study groups, there was no statistically significant difference in the follow up scores between the groups. At follow up the memory rating improved and none of the patients in either group had a dysfunctional rating score of three.Conclusion:The study has shown that there is an overall neurocognitive impairment associated with both alcohol addiction as well as opioid dependence at baseline when compared to the general population, but the magnitude of neurocognitive improvement is more in opioid dependence syndrome in this current study at follow up when compared to alcohol dependence patients. Thus, the results support our main hypothesis of higher chances of improvement in cognitive performance with therapy in patients of opioids dependency, evident as early as week four or one month of therapy.A cross-sectional survey was conducted among adult psychiatric outpatients with depressive disorders at a teaching hospital in Kuala Lumpur for 10 months. Sociodemographic and illness-related data were gathered. Two questionnaires, Mood Disorder Insight Scale (MDIS) and Internalized Stigma of Mental Illness Scale (ISMI), were administered.

Abstract- Poster

Introduction-The utility of cognitive assessment has increasingly come to fore because the diagnostic categories in psychiatry are for the most part syndromal. As a consequence there is wide variation in the degree of disability and handicap within the same diagnostic category. PGI BBD is a validated tool for assessment of cognitive deficits and its utilisation will help in quantification of disability and rehabilitation.Method–The study was conducted at Tertiary care hospital. 200 male inpatients belonging to the 5 diagnostic groups- Alcohol Dependence Syndrome, Anxiety Disorders, Depressive Disorders, Bipolar Affective Disorder, Schizophrenia were included in the study after written informed consent. Analysis was performed by the SPSS version 20.0. Comparison among the five diagnostic groups was done using ANOVA and Tukey Post hoc pair wise comparison.Result-Patients of Alcohol Dependence Syndrome had impairment in remote memory, visual retention and recognition, performance quotient, verbal quotient and percepto motor functioning. Patients of Anxiety Disorder had deficit in attention concentration, verbal memory. Patients of Depressive Disorder had deficit in attention and concentration, immediate and delayed recall, verbal memory, comprehension and percepto motor functioning. Patient of BPAD had deficit in attention and concentration, visual memory. Patients of Schizophrenia had deficit in verbal and visual memory and performance tests.Conclusion:Patients in all diagnostic groups had significant impairment of cognitive function even while in remission when they were about to be discharged from hospital. Theses deficit will result in occupational impairment and cognitive retraining is necessary.

ニューロステロイドによるマウス空間記憶形成の制御とその日周変化

ニューロステロイドによるマウス空間記憶形成の制御とその日周変化

Future-Based Persistent Spatial Data Structure for NVM-Based Manycore Machines

R-trees have been popular for their support of multidimensional data and high-performing queries. FBR-tree is the state-of-the-art concurrent variant of the R-tree for Intel DC Persistent Memory (DCPM). However, its adoption on manycore servers is impeded by concurrency limitations due to lengthy, lock-based synchronization, including structure modification operations, split and merge. Additionally, emerging DCPM-based machines are equipped with multiple CPU sockets, forming a non-uniform memory access (NUMA) architecture. FBR-tree’s lack of NUMA-awareness induces further performance overhead from remote memory accesses. In this paper, we propose MPR-tree, a concurrent, NUMA-aware and persistent future-based R-tree for DCPM servers. MPR-tree focuses on insert operations due to their laborious nature. MPR-tree relies on per-thread local future objects and a global R-tree. To introduce NUMA-awareness and minimize remote memory accesses, MPR-tree adopts per-socket dedicated asynchronous evaluate threads to checkpoint future objects to the global R-tree. MPR-tree employs an in-memory hash table to mitigate the read overhead of key searches over the future objects. We implemented MPR-tree atop FBR-tree and evaluated its performance on a server with 40 physical cores for insert and lookup queries, and it showed that MPR-tree outperforms FBR-tree on average by 2× on log10 scale.

PKMζ Maintains Remote Contextual Fear Memory by Inhibiting GluA2-Dependent AMPA Receptor Endocytosis in the Prelimbic Cortex

Fear memories allow animals to recognize and adequately respond to dangerous situations. The prelimbic cortex (PrL) is a crucial node in the circuitry that encodes contextual fear memory, and its activity is central for fear memory expression over time. However, while PrL has been implicated in contextual fear memory storage, the molecular mechanisms underlying its maintenance remain unclear. Protein kinase M zeta (PKMζ) is a persistently active enzyme which has been shown to maintain many forms of memories by inhibiting the endocytosis of GluA2-containing AMPA receptors. Therefore, we hypothesized that PKMζ action upon GluA2-containing AMPARs could be a mechanism for contextual fear memory maintenance in the PrL. To test this hypothesis, we trained rats in a contextual fear conditioning (CFC) paradigm and administered intra-PrL infusions of the PKMζ inhibitor ZIP, the GluA2-dependent endocytosis inhibitor GluA23Y or the inactive peptide GluA23Y(s), either two or twenty days after conditioning, and assessed long-term memory retention twenty-four hours later. We found that acute inhibition of GluA2-dependent AMPAR endocytosis in the PrL does not affect recent or remote contextual fear memory maintenance. Also, PKMζ inhibition in the PrL does not impair the maintenance of recent contextual fear memory. However, we found that inhibition of prelimbic PKMζ at a remote time point disrupts contextual fear memory maintenance, and that blocking GluA2-dependent removal of AMPARs prevents this impairment. Our results confirm the central role of PrL in fear memory and identify PKMζ-induced inhibition of GluA2-containing AMPAR endocytosis as a key mechanism governing remote contextual fear memory maintenance.

Predictive Factors for Conversion to Dementia in Individuals with Early-Onset Mild Cognitive Impairment

Introduction: There is little research on factors predicting conversion to dementia in early-onset mild cognitive impairment (eoMCI), a transitional stage between healthy ageing and dementia in individuals below the age of 65. We aimed to examine whether sociodemographic and clinical factors at initial presentation predicted dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the UK. Methods: This is a retrospective case note study of individuals diagnosed with eoMCI between 2000 and 2013 at the Younger Person’s Memory Service (YPMS) in Leicestershire, England. Data collected at assessment included social factors, demographic characteristics, and medical and psychiatric history, as well as standardized cognitive assessment scores. Variables were analysed using χ² or independent sample t tests to identify associations. A Cox regression survival analysis was done to identify predictive factors for dementia conversion. An ROC analysis for total CAMCOG was used to investigate sensitivity and specificity for dementia converters versus non-converters. Results: Out of 531 subjects who attended YPMS, 65 patients were given a diagnosis of eoMCI (47.7% female; mean age 56.4 ± 7.54 years). Of these, 21 (32.3%) converted to dementia during their course within the service. Comparison between subgroups revealed a significant association between dementia conversion and higher years of education and lower MMSE and CAMCOG (total and subscale) scores at baseline. Smoking history, alcohol use, or medical history such as diabetes or heart disease were not associated with conversion. Cox regression survival analysis showed higher education in years and lower total CAMCOG scores were significant predictors for conversion. Lower scores on the recent memory, remote memory, learning memory, and executive function subscales of the CAMCOG were also significant predictors for conversion. ROC curve analysis for total CAMCOG demonstrated that the best detection of dementia converters can be achieved with a cutoff score of 90.5/107 (sensitivity of 76.2% and specificity of 68.2%). Area under the curve was 0.808 (95% CI: 0.697–0.920). Conclusion: More years in education and lower cognitive scores on CAMCOG at initial assessment are associated with progression to dementia from eoMCI. Further research is required to explore these predictive factors more.

Cathodal transcranial direct current stimulation on the prefrontal cortex applied after reactivation attenuates fear memories and prevent reinstatement after extinction

BackgroundIn the last decade, pharmacological strategies targeting reconsolidation after memory retrieval have shown promising efforts to attenuate persistent memories and overcome fear recovery. However, most reconsolidation inhibiting agents have not been approved for human testing. While non-invasive neuromodulation can be considered an alternative approach to pharmacological treatments, there is a lack of evidence about the efficacy of these technologies when modifying memory traces via reactivation/reconsolidation mechanism. ObjectiveIn this study, we evaluate the effect of cathodal (c-tDCS) and anodal (a-DCS) transcranial direct current stimulation applied after memory reactivation and extinction in rats. MethodsMale Wistar rats were randomly assigned into three groups: one sham group, one anodal tDCS group, and one cathodal tDCS group (500 μA, 20 min). Reconsolidation and extinction of fear memories were evaluated using a contextual fear conditioning. ResultsOur results showed that c-tDCS and a-tDCS after memory reactivation can attenuate mild fear memories. However, only c-tDCS stimulation prevented both fear expression under strong fear learning and fear recovery after a reinstatement protocol without modification of learning rate or extinction retrieval. Nevertheless, the remote memories were resistant to modification through this type of neuromodulation. Our results are discussed considering the interaction between intrinsic excitability promoted by learning and memory retrieval and the electric field applied during tDCS. ConclusionThese results point out some of the boundary conditions influencing the efficacy of tDCS in fear attenuation and open new ways for the development of noninvasive interventions aimed to control fear-related disorders via reconsolidation.

Continuous theta-burst stimulation over the right dorsolateral prefrontal cortex disrupts fear memory reconsolidation in humans

SummaryContinuous theta-burst stimulation (cTBS), a non-invasive brain stimulation technique, can induce long-lasting changes in synaptic plasticity, vital for memory reconsolidation. For this study, a total of 170 participants completed four experiments by a randomized controlled design. Succeeding fear conditioning, the subjects received cTBS over the right dorsolateral prefrontal cortex (dlPFC) or vertex (control) with or without exposure to the conditioned stimulus to reactivate the original fear memory, and then underwent fear response tests. Compared with cTBS over the vertex and without memory reactivation, only cTBS over the right dlPFC after reactivation decreased the fear response for both recent and remote fear memories. This procedure was effective only during the reconsolidation window. The disruptive effect of cTBS over the right dlPFC on fear memory reconsolidation was delay-dependent. These findings demonstrate that cTBS time-dependently and delay-dependently prevents the return of fear and may have clinical potential for treating fear-related disorders.

Deterministic Constant-Amortized-RMR Abortable Mutex for CC and DSM

The abortable mutual exclusion problem, proposed by Scott and Scherer in response to the needs in real-time systems and databases, is a variant of mutual exclusion that allows processes to abort from their attempt to acquire the lock. Worst-case constant remote memory reference algorithms for mutual exclusion using hardware instructions such as Fetch&Add or Fetch&Store have long existed for both cache coherent (CC) and distributed shared memory multiprocessors, but no such algorithms are known for abortable mutual exclusion. Even relaxing the worst-case requirement to amortized, algorithms are only known for the CC model. In this article, we improve this state of the art by designing a deterministic algorithm that uses Fetch&Store to achieve amortized O (1) remote memory reference in both the CC and distributed shared memory models. Our algorithm supports Fast Abort (a process aborts within six steps of receiving the abort signal) and has the following additional desirable properties: it supports an arbitrary number of processes of arbitrary names, requires only O (1) space per process, and satisfies a novel fairness condition that we call Airline FCFS . Our algorithm is short with fewer than a dozen lines of code.

The persistence of remote visual semantic memory following ocular blindness

Subjects with complete ocular blindness in both eyes provide a unique opportunity to study the long-term durability of visual semantic memory. In this cross-sectional study we recruited eleven subjects who had acquired blindness for between 1 and 36 years. For comparison, we studied four subjects with congenital blindness and seventeen age- and sex-matched sighted control subjects. We administered ten forced-choice questionnaires that probed one auditory category and four visual categories, namely object shape and size; object hue and lightness; word and letter shape; and the shape and features of famous faces. Subjects with congenital blindness performed worse than controls on all visual categories, but nevertheless performed better than chance on object structure or colour, suggesting that the answers to some questions about visual properties can be derived from haptic or non-visual semantic information. Subjects with acquired blindness performed similarly to controls on all categories except for facial memory, particularly for facial features. We conclude that there is a substantial “permastore” of visual semantic memory but that facial memories are less durable, perhaps indicating that they are either less over-learned or more dependent on visual representations than other forms of visual object information.